Objective: Intraocular hemorrhage is an adverse event that can lead to impaired visual acuity. Therapy with antiplatelet agents and anticoagulants may increase the risk of intraocular hemorrhage. However, because the frequency is low, studies on the risk of intraocular hemorrhages with these medicinal products, especially with combination therapy, are limited. This study aimed to investigate the occurrence of intraocular hemorrhages with monotherapy and combination therapy with antithrombotic medicinal products and anticoagulants by analyzing a large volume of pharmacovigilance data.
Methods: A signal of intraocular hemorrhage with oral antithrombotic medicinal products and anticoagulants was detected using a Japanese database of adverse drug reaction reports for the period from April 2004 to March 2022. In addition, differences between young and elderly patients, influencing factors, and the time to onset of the adverse reaction after the start of therapy with antithrombotic medicinal products and anticoagulants were analyzed.
Results: Acetylsalicylic acid (aspirin), clopidogrel, warfarin, apixaban and rivaroxaban (with the exception of ticagrelor, ticlopidine, prasugrel, dabigatran and edoxaban) caused intraocular hemorrhage in monotherapy. In combination therapy, dual therapy (acetylsalicylic acid (aspirin) + P2Y12 inhibitors, warfarin, direct oral anticoagulants and P2Y12 inhibitors + warfarin) and triple therapy (acetylsalicylic acid (aspirin) + P2Y12 inhibitors + warfarin), a signal of intraocular hemorrhage was detected. Intraocular hemorrhage was observed in young patients receiving acetylsalicylic acid (aspirin) monotherapy and in elderly patients receiving warfarin monotherapy and combination therapy. Risk factors were diabetes mellitus in patients receiving prasugrel, and the use of medicinal products for intravitreal injections and posterior sub-Tenon injections together with some antithrombotic medicinal products and anticoagulants. The mean time to onset of intraocular hemorrhage after the start of monotherapy with acetylsalicylic acid (aspirin), clopidogrel, warfarin or rivaroxaban was 90 days.
Summary: monotherapy with some antithrombotic medicinal products and anticoagulants, and combination therapy using acetylsalicylic acid (aspirin), P2Y12 inhibitors and warfarin carry a potential risk of intraocular hemorrhage. Particular attention should be paid to the occurrence of intraocular hemorrhages in young patients using acetylsalicylic acid (aspirin) and in elderly patients using warfarin during the first 90 days of use of antithrombotic medicinal products and anticoagulants.
Conclusion
Therefore, the potential risk of intraocular hemorrhage increases during monotherapy with acetylsalicylic acid (aspirin), clopidogrel, warfarin, apixaban, and rivaroxaban and during combination therapy with most antithrombotic medicinal products and anticoagulants (for example, dual antithrombotic therapy). The use of acetylsalicylic acid (aspirin) in young patients and of warfarin in elderly persons during the first 90 days of therapy with antithrombotic medicinal products and anticoagulants should be considered a risk factor for intraocular hemorrhage. These results may help internists, ophthalmologists, pharmacists, and other health care professionals predict and manage the occurrence of intraocular hemorrhage during monotherapy with antithrombotic medicinal products and anticoagulants and during combination therapy.
The full text of the signal on the occurrence of intraocular hemorrhages with monotherapy or combination therapy with antithrombotic medicinal products and anticoagulants can be found at the link:
Occurrence of intraocular hemorrhages under monotherapy or combination therapy of antiplatelets and anticoagulants using the Japanese Adverse Drug Event Report database Junko Tanaka, Takenao Koseki, Kohsuke Sekido, Masashi Kimata, Yasuki Ito and Shigeki Yamada
